299MO - Efficacy and safety of entrectinib in an Asian population with <italic>NTRK</italic> fusion-positive (fp) solid tumours or <italic>ROS1</italic>-fp NSCLC

Background

Entrectinib efficacy was established in an integrated analysis of 3 trials (ALKA-372-001 EudraCT 2012-000148-88; STARTRK-1 NCT02097810; STARTRK-2 NCT02568267) in adult pts with NTRK-fp tumours (objective response rate [ORR] 63.5%; data cutoff 31 Oct 2018) and ROS1-fp NSCLC (ORR 73.4%; data cutoff 1 May 2019). We conducted a subanalysis to confirm if entrectinib efficacy and safety in Asian patients is consistent with the total populations.

Methods

Enrolled pts were NTRK and ROS1 TKI naïve with locally advanced/metastatic solid tumours or NSCLC, with/without baseline CNS metastases. Tumour response was assessed by blinded independent central review (BICR) using RECIST v1.1 after 4 wks and every 8 wks thereafter. Primary endpoints were ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety.

Results

The Asian efficacy-evaluable populations comprised 13 pts (17.6% of total population) with NTRK-fp tumours (breast, 1; colon, 2; NSCLC, 4; MASC, 4; sarcoma, 2) and 41 pts (43.6% of total population) with ROS1-fp NSCLC. Overall and intracranial efficacy outcomes are presented (Table). In pts with/without baseline CNS metastases (investigator assessed) overall ORR was 75.0% (3/4)/66.7% (6/9) for NTRK-fp tumours and 75.0% (15/20)/81.0% (17/21) for ROS1-fp NSCLC. In the Asian safety-evaluable populations, grade 1–2 and 3–4 treatment-related adverse events (TRAEs) were reported by 50.0% and 31.8% of pts with NTRK-fp tumours (n=22), and 57.1% and 33.0% of pts with ROS1-fp NSCLC (n=91). There were no grade 5 TRAEs. Discontinuations/dose reductions due to TRAEs occurred in 4.5%/27.3% of pts with NTRK-fp tumours and 6.6%/27.5% of pts with ROS1-fp NSCLC.

Conclusions

Entrectinib treatment achieved high response rates with a manageable safety profile in Asian pts with NTRK-fp solid tumours or ROS1-fp NSCLC, with/without baseline CNS metastases, consistent with findings in the total populations. Table: 299MO

Median follow-up: NTRK-fp, 14.8 mos; ROS1-fp 19.8 mos *Baseline CNS metastases by BICR; ^†Range for 3 pts NE, not estimable

Clinical trial identification

ALKA-372-001 (EudraCT 2012-000148-88); STARTRK-1 (NCT02097810); STARTRK-2 (NCT02568267).

Editorial acknowledgement

Third-party medical writing assistance, under the direction of the authors, was provided by Cassidy Bayley, PhD, of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

D.S.W. Tan: Honoraria (self): Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli Lilly, and Loxo; Research grant/Funding (institution): Novartis, Bayer, AstraZeneca, Pfizer, GlaxoSmithKline; Travel/Accommodation/Expenses: Novartis, Boehringer Ingelheim, Celgene, Merck, Pfizer, Roche, Takeda. M-J. Ahn: Honoraria (self): AstraZeneca, Eli Lilly, Takeda, Roche, MSD; Advisory/Consultancy: AstraZeneca, Eli Lilly, Takeda, Roche, MSD, Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, Alpha Pharmaceutical, Progeneer. C-H. Chiu: Honoraria (self): Pfizer, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Roche; Advisory/Consultancy: AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai Pharmaceutical, MSD, Novartis, Ono Pharmaceutical, Roche. Y. Ohe: Honoraria (self): AstraZeneca, Chugai, Eli Lilly, Ono, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho Pharmaceutical, Nippon Kayaku, Kyowa Hakko Kirin; Advisory/Consultancy: AstraZeneca, Chugai Pharmaceutical, Ono, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku; Research grant/Funding (institution): AstraZeneca, Chugai Pharmaceutical, Lilly, Ono, BMS, Kyorin, Dainippon-Sumitomo, Pfizer, Taiho Pharmaceutical, Novartis, Kissei Pharmaceutical, Ignyta, Takeda, Daiichi-Sankyo, Janssen, Loxo; Officer/Board of Directors: JSMO, JLCS. H.H.F. Loong: Advisory/Consultancy: Boehringer-Ingelheim, Celgene, Eli Lilly, Novartis, Merck, Roche, Takeda; Speaker Bureau/Expert testimony: AbbVie, Bayer, Eisai, Eli Lilly, Guardant Health, Novartis; Travel/Accommodation/Expenses: Bayer, MSD, Novartis, Pfizer; Research grant/Funding (institution): MSD, Mundipharma, Novartis. S-W. Kim: Advisory/Consultancy: AstraZeneca, Boehringer-Ingelheim, Lilly, Novartis; Research grant/Funding (self): AstraZeneca. M. Takeda: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Novartis Pharma, Ono Pharmaceutical. Y-C. Li: Advisory/Consultancy: Roche, AstraZeneca, Foundation Medicine, Boehringer Ingelheim, Lilly Oncology, Merck, Pfizer, Novartis, Takeda, MSD; Research grant/Funding (self): Roche; Travel/Accommodation/Expenses: Roche, Taiho Pharmaceutical, Eisai, Sanomic, Xcelom, Takeda, AstraZeneca, MSD, Boehringer Ingelheim, Pfizer, Mundipharma. A. Cheng: Research grant/Funding (institution): Roche. T. Hida: Honoraria (self): Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Novartis, Bristol-Meyers Squibb, Kissei Pharmaceutical, Taiho Pharmaceutical, Pfizer, MSD, Takeda; Research grant/Funding (institution): Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Nippon Boehringer Ingelheim, Novartis, Bristol-Meyers Squibb, Kissei Pharmaceutical, Taiho Pharmaceutical, Pfizer, MSD, Takeda, Merck, Abbvie, Daiichi Sankyo, Astellas, Janssen. D-W. Kim: Research grant/Funding (institution): Alpha Biopharma, Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche, Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen, Daiichi-Sankyo. N. Nogami: Honoraria (self): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb, Ono Pharmaceutical, Kyowa Hakko Kirin, Taiho, Chugai Pharmaceutical, Eli Lilly, Boehringer Ingelheim. H. Tanaka: Honoraria (self): Pfizer, Novartis, Bristol-Myers Squibb, Eli Lilly, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical; Research grant/Funding (institution): Bristol-Myers Squibb, Eli Lilly, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, Ono Pharmaceutical. S. Osborne, R. Freund: Full/Part-time employment: F. Hoffmann-La Roche. D. Chen: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech. T. Seto: Honoraria (self): Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kyowa Hakko Kirin, MSD, Boehringer Ingelheim, Novartis, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Takeda, Thermo Fisher Scientific; Research grant/Funding (institution): AbbVie, AstraZeneca, Bayer Yakuhin, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, Kissei Pharmaceutical, Loxo, MSD, Boehringer Ingelheim, Novartis, Pfizer, Takeda; Full/Part-time employment: Precision Medicine Asia. All other authors have declared no conflicts of interest.